Azido- and chlorido-cobalt complex as carrier-prototypes for antitumoral prodrugs.

Cobalt(III) complexes are well-suited systems for cytotoxic drug release under hypoxic conditions. Here, we investigate the effect of cytotoxic azide release by cobalt-containing carrier-prototypes for antitumoral prodrugs. In addition, we study the species formed after reduction of Co(3+) → Co(2+) in the proposed models for these prodrugs. Three new complexes, [Co(III)(L)(N3)2]BF4(1), [{Co(II)(L)(N3)}2](ClO4)2(2), and [Co(II)(L)Cl]PF6(3), L=[(bis(1-methylimidazol-2-yl)methyl)(2-(pyridyl-2-yl)ethyl)amine], were synthesized and studied by several spectroscopic, spectrometric, electrochemical, and crystallographic methods. Reactivity and spectroscopic data reveal that complex 1 is able to release N3(-) either after reduction with ascorbic acid, or by ambient light irradiation, in aqueous phosphate buffer (pH6.2, 7.0 and 7.4) and acetonitrile solutions. The antitumoral activities of compounds 1-3 were tested in normoxia on MCF-7 (human breast adenocarcinoma), PC-3 (human prostate) and A-549 (human lung adenocarcinoma epithelial) cell lines, after 24h of exposure. Either complexes or NaN3 presented IC50 values higher than 200 µM, showing lower cytotoxicity than the clinical standard antitumoral complex cisplatin, under the same conditions. Complexes 1-3 were also evaluated in hypoxia on A-549 and results indicate high IC50 data (>200 µM) after 24h of exposure. However, an increase of cancer cell susceptibility to 1 and 2 was observed at 300 µM. Regarding complex 3, no cytotoxic activity was observed in the same conditions. The data presented here indicate that the tridentate ligand L is able to stabilize both oxidation states of cobalt (+3 and +2). In addition, the cobalt(III) complex generates the low cytotoxic cobalt(II) species after reduction, which supports their use as as carrier prototypes for antitumoral prodrugs.

Synthesis and Characterization of Cobalt(III), Nickel(II) and Copper(II) Mononuclear Complexes with the Ligand 1,3-bis[(2-aminoethyl)amino]-2-propanol and Their Catalase-Like Activity.

In this work, we present the synthesis and characterization of two new mononuclear complexes with the ligand 1,3-bis[(2-aminoethyl)amino]-2-propanol (HL), [Co(L)(H2O)](ClO4)2 (1), [Ni(HL)](ClO4)2 (2), as well as the known complex [Cu(HL)](ClO4)2 (3) for comparison. Their abilities to catalyze the dismutation of H2O2 and the oxidation of cyclohexane were investigated. The complexes were characterized by X-ray diffraction, elemental analysis, electronic and infrared spectroscopy, cyclic voltammetry, electrospray ionization mass spectrometry (ESI-MS) and conductivity measurements. The X-ray structures showed that the nickel (2) and copper (3) complexes are tetracoordinated, with the metal ion bound to the nitrogen atoms of the ligand. On the other hand, the cobalt complex (1) is hexacoordinated, possessing additional bonds to the alkoxo group of the ligand and to a water molecule. Neither of the complexes was able to catalyze the oxidation of cyclohexane, but all of them exhibited catalase-like activity, following Michaelis-Menten kinetics, which suggest resemblance with the catalase natural enzymes. The catalytic activity followed the order: [Ni(HL)](ClO4)2 (2) > [Cu(HL)](ClO4)2 (3) > [Co(L)(H2O)](ClO4)2 (1). As far as we know, this is the first description of a nickel complex presenting a significant catalase-like activity.